Biomedical subjects

T Salminen

Publications and source records attributed to T Salminen.

At least 19 recordsLinked to original sources

PubMed2007

Medical history, cigarette smoking and risk of acoustic neuroma: an international case-control study.

Acoustic neuroma (vestibular schwannoma) is a benign tumor of the vestibulocochlear nerve. Its recorded incidence is increasing but risk factors for this tumor have scarcely been investigated. We conducted a population-based case-control study of risk factors for acoustic neuroma in the UK and Nordic countries, including 563 cases and 2,703 controls. Tumor risk was analyzed in relation to medical history and cigarette smoking. Risk of acoustic neuroma was significantly raised in parous compared with nulliparous women (OR = 1.7, 95% CI: 1.1-2.6), but was not related to age at first birth or number of children. Risk was not associated with a history of allergic disease, past head injury, past diagnosis of a neoplasm or birth characteristics, but was significantly raised for past diagnosis of epilepsy (OR = 2.5, 95% CI: 1.3-4.9). Tumor risk was significantly reduced in subjects who had ever regularly smoked cigarettes (OR = 0.7, 95% CI: 0.6-0.9), but the reduction applied only to current smokers (OR = 0.5, 95% CI: 0.4-0.6), not ex-smokers (OR = 1.0, 95% CI: 0.8-1.3). The reduced risk of acoustic neuroma in smokers and raised risk in parous women might relate to sex hormone levels, or smoking might suppress tumor growth, but effects of parity and smoking on timing of diagnosis of the tumor are also a potential explanation. The raised risk in relation to past diagnosis of epilepsy might be a surveillance artefact or imply that epilepsy and/or antiepileptic medication use predispose to acoustic neuroma. These findings need replication by other studies and possible mechanisms need to be clarified.

Adolescent↗

PubMed2006

Validation of short term recall of mobile phone use for the Interphone study.

AIM: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. METHODS: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. RESULTS: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. CONCLUSIONS: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Case-Control Studies↗

PubMed2005

Mobile phone use and risk of acoustic neuroma: results of the Interphone case-control study in five North European countries.

There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population-based case-control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7-1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR = 1.8, 95% CI: 1.1-3.1). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out.

Case-Control Studies↗

PubMed2001

N-in-one determination of retention factors for drugs by immobilized artificial membrane chromatography coupled to atmospheric pressure chemical ionization mass spectrometry.

Immobilized artificial membrane (IAM) chromatography is widely used in drug discovery for ranking the absorption properties of drug candidates. In this work an IAM chromatography method using atmospheric pressure chemical ionization mass spectrometric detection (IAM/APCI-MS) was developed for the determination of log k(IAM) values for a mixture of compounds (9-in-one). Values were calculated from isocratic runs (0, 10, 20, 30, 35% acetonitrile) in both positive and negative modes. Good correlation (r(2) = 0.97) was achieved for n-in-one results obtained with ammonium acetate buffer and mass spectrometry, compared with the traditional method involving single compound analysis with phosphate buffered saline and an ultraviolet detector. A gradient elution method providing fast determination of relative log k(IAM) values in a single IAM/APCI-MS run was demonstrated for the same compounds.

Chromatography, High Pressure Liquid↗

PubMed2001

A cell surface amine oxidase directly controls lymphocyte migration.

Lymphocytes leave the blood using a sequential adhesion cascade. Vascular adhesion molecule-1 (VAP-1) is a surface-expressed endothelial glycoprotein, which belongs to a distinct subgroup of monoamine oxidases. We show here that catalytic activity of VAP-1 on primary endothelial cells directly regulates lymphocyte rolling under defined laminar shear. VAP-1 seems to bind to a primary amino group presented on the lymphocyte surface and oxidatively deaminate it in a reaction, which results in the formation of a transient covalent bond between the two cell types. Instead, soluble reaction products (aldehydes and hydrogen peroxide) are not needed for the VAP-1-dependent rolling. Enzymatic regulation of lymphocyte adhesion to endothelium provides a previously unrecognized rapid way of controlling the extravasation process.

Aldehydes↗

PubMed2001

The effect of age and density of the breast on the sensitivity of breast cancer diagnostic by mammography and ultasonography.

PURPOSE: We studied which, age of the patient or density of the breast accounts for the sensitivity of mammography and ultrasonography (US). Furthermore we studied whether the overall impression on the density of the breast or the density in tumour area accounts for the sensitivity of mammography and ultrasonography. MATERIALS AND METHODS: The material consisted of 572 consecutive histologically and 5 cytologically verified breast cancer cases. Mammography and US examinations were performed immediately before breast cancer operations and information on the findings were received from the original patient files and classified as malignant or benign. The density of breast parenchyma to fatty, mixed or dense in total breast and separately in tumour area was defined by a radiologist group from the original mammograms by comparing to model mammograms. The sensitivity (Se) of mammography and US was compared in 3 age groups (26-49, 50-59 and 60-92) and in the different density classes. RESULTS: Sensitivity of mammography increased by age (density-adjusted OR = 0.2, 95%, CI 0.1-0.5) in age group 26-49 compared to age group 60-92) and with fattiness of the breast (age-adjusted OR= 0.4, 95%, CI 0.1-1.0 for dense breast parenchyma in tumour area compared to fatty breast). Sensitivity of US was inversely related to age (density-adjusted OR = 2.3, 95%, CI 1.0-5.2 in age group 26-49 compared to age group 60-92) and directly related with fattiness of breast (age-adjusted OR = 0.5, 95%, CI 0.2-0.9 by dense breast parenchyma in tumour area compared to fatty breast). Density in the tumour area compared to total breast density was related only mariginally better sensitivity both of mammography (0.4 vs. 0.6) and of US (0.5 vs. 0.6). CONCLUSION: Sensitivity of both mammography and sensitivity of US are independently related both to the age of the patient and to the density of the breast. The effect of age is inverse and that of density parallel between mammography and US on sensitivity. The effect of overall breast density was close to the effect of density at the site of the tumour on the sensitivity of both mammography and US.

Adult↗

PubMed2001

Amplification of c-myc oncogene by chromogenic and fluorescence in situ hybridization in archival breast cancer tissue array samples.

Fluorescence in situ hybridization (FISH) is currently considered to be the most specific and sensitive method for detection of oncogene amplifications in human tumor samples. However, FISH requires fluorescence microscopy, which is tedious and does not allow histopathologic evaluation of the cells and tissues examined. Here we compared FISH with the newly developed chromogenic in situ hybridization (CISH), which uses peroxidase enzyme for probe detection instead of fluorescent dyes. CISH was found to be highly concordant with FISH in a tissue array series of 177 archival breast cancer samples. This was true both when comparing CISH with single-color and two-color FISH, the latter including the chromosome 8 centromere probe as reference (the kappa coefficients were 0.67 and 0.76, respectively). Clinicopathologic correlations of c-myc amplification as detected by FISH and CISH were generally the same. By both methods, c-myc amplification was significantly associated with high histologic grade, negative progesterone receptor status, DNA aneuploidy, and high S-phase fraction. c-myc amplification was strongly associated with poor distant metastasis-free survival when amplification was detected by CISH (p = 0.0013), but this association was weaker when FISH was used (p = 0.16 for two-color FISH and p = 0.065 for single-color FISH). These data suggest that CISH is at least as sensitive and specific as FISH in the detection of oncogene amplification in human tumor samples. The possibility for concomitant tissue architecture evaluation using an ordinary transmitted light microscope may favor the use of CISH over FISH in oncogene amplification detection in large tumor series, and tissue arrays and, ultimately, in routine clinical diagnostics.

Archives↗

PubMed2001

Amplification of c-myc by fluorescence in situ hybridization in a population-based breast cancer tissue array.

A total of 261 primary breast carcinomas were analyzed for amplification of the c-myc oncogene by fluorescence in situ hybridization performed on tumor tissue array samples. Results were compared with individual clinicopathologic and follow-up data. Thirty-eight (14.6%) of the tumors showed c-myc gene amplification (defined as two or more additional copies of c-myc gene in relation to the number of chromosome 8 centromere). The reproducibility of fluorescence in situ hybridization assay (defined by hybridization with two different myc probes) was good (kappa coefficient 0.402). Statistically significant associations were found between c-myc amplification and DNA aneuploidy (P =.0011), and progesterone receptor negativity (P =.0071), and c-myc amplification also tended to be associated with high histologic grade (P =.064), positive axillary nodal status (P =.080), and a high S-phase fraction (P =.052). c-myc amplification was not significantly associated with overall survival of patients with invasive cancer (P =.32). These data from a population-based tumor material suggest that c-myc amplification is a feature of aggressive breast cancers, but that it is unlikely to be a clinically useful prognostic factor.

Aneuploidy↗

PubMed2001

The visibility of cancer on previous mammograms in retrospective review.

AIM: To study how many tumours were visible in restrospect on mammograms originally reported as normal or benign in patients coming to surgery with proven breast cancer. The effect of making the pre--operative mammogram available was also assessed. MATERIALS AND METHODS: Three hundred and twenty initial mammograms of consecutive new breast cancer cases were analysed by a group of radiologists in the knowledge that all patients were later diagnosed with breast cancer. The films were read twice, first without and then with the later (pre-operative) mammograms available. The parenchymal density in the location of the tumour was classified as fatty, mixed or dense, and the tumours were classified as visible or not visible. The reasons for the invisibility of the tumour in the earlier examination were analysed. RESULTS: Fourteen per cent (45) of cancers were retrospectively visible in earlier mammograms without the pre-operative mammograms having been shown, and 29% (95) when pre-operative mammograms were shown. Breast parenchymal density decreased with age and the visibility of tumours increased with age. When considered simultaneously, the effect of age (over 55 vs under 55) was greater (OR = 2.9) than the effect of density (fatty vs others) (OR = 1.5). The most common reasons for non-detection were that the lesion was overlooked (55%), diagnosed as benign (33%) or was visible only in one projection (26%). Growing density was the most common (37%) feature of those lesions originally overlooked or regarded as benign. CONCLUSIONS: Tumours are commonly visible in retrospect, but few of them exhibit specific signs of cancer, and are recognized only if they grow or otherwise change. It is not possible to differentiate most of them from normal parenchymal densities. Saarenmaa, I. (2001). Clinical Radiology56, 40-43.

Adult↗

PubMed2001

Validity of radiological examinations of patients with breast cancer in different age groups in a population based study.

By studying which radiological examinations had been performed before breast cancer operations the aim was to assess, how much benefit ultrasonography (US) and fine or core needle biopsy (FNAB, CNB) gave in addition to mammography, and whether the sensitivity of these examinations varied with the age of the patient. There were 659 consecutive histologically and six cytologically verified breast cancer cases included in the study. Information on mammography, US and FNAB findings were retrieved from the original patient files and classified as malignant or benign. The sensitivity (Se) of these was compared in three age groups (26-49, 50-59 and 60-92). Seventeen (3%) tumours had operations without any radiological examination and 73 (11%) without cytological or histological verification. The sensitivity of mammography (Se=0.92) was statistically significantly higher than the sensitivity of FNAB (Se=0.85, P=0.002) or US (Se=0.86, P=0.003). The sensitivity of mammography increased with age; US sensitivity was slightly higher amongst younger than older patients; the sensitivity of FNAB did not depend on the age of the patient. The sensitivity using a cutoff level of class 5 for mammography was higher (50% typical malignant findings) than for US (45%) or FNAB (30%). Among cases with benign mammographic finding (classes 1-2), the US finding was malignant (classes 3-5) in 4% and FNAB was malignant in 7%. Mammography is a reliable method of breast examination especially for women over 50 years of age. Ultrasonography is beneficial, particularly in younger women, but it is mainly performed as a complementary examination to a mammography and therefore could not be evaluated as an independent examination. FNAB and CNB results were not related to the age of the patient.

Journal Article↗

PubMed2001

Molecular mechanism for agonist-promoted alpha(2A)-adrenoceptor activation by norepinephrine and epinephrine.

We present a mechanism for agonist-promoted alpha(2A)-adrenergic receptor (alpha(2A)-AR) activation based on structural, pharmacological, and theoretical evidence of the interactions between phenethylamine ligands and alpha(2A)-AR. In this study, we have: 1) isolated enantiomerically pure phenethylamines that differ both in their chirality about the beta-carbon, and in the presence/absence of one or more hydroxyl groups: the beta-OH and the catecholic meta- and para-OH groups; 2) used [(3)H]UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine; agonist] and [(3)H]RX821002 [2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline; antagonist] competition binding assays to determine binding affinities of these ligands to the high- and low-affinity forms of alpha(2A)-AR; 3) tested the ability of the ligands to promote receptor activation by measuring agonist-induced stimulation of [(35)S]GTPgammaS binding in isolated cell membranes; and 4) used automated docking methods and our alpha(2A)-AR model to predict the binding modes of the ligands inside the alpha(2A)-AR binding site. The ligand molecules are sequentially missing different functional groups, and we have correlated the structural features of the ligands and ligand-receptor interactions with experimental ligand binding and receptor activation data. Based on the analysis, we show that structural rearrangements in transmembrane helix (TM) 5 could take place upon binding and subsequent activation of alpha(2A)-AR by phenethylamine agonists. We suggest that the following residues are important in phenethylamine interactions with alpha(2A)-AR: Asp113 (D(3.32)), Val114 (V(3.33)), and Thr118 (T(3.37)) in TM3; Ser200 (S(5.42)), Cys201 (C(5.43)), and Ser204 (S(5.46)) in TM5; Phe391 (F(6.52)) and Tyr394 (Y(6.55)) in TM6; and Phe411 (F(7.38)) and Phe412 (F(7.39)) in TM7.

Adrenergic Agonists↗

PubMed1999

Three-dimensional models of alpha(2A)-adrenergic receptor complexes provide a structural explanation for ligand binding.

We have compared bacteriorhodopsin-based (alpha(2A)-AR(BR)) and rhodopsin-based (alpha(2A)-AR(R)) models of the human alpha(2A)-adrenengic receptor (alpha(2A)-AR) using both docking simulations and experimental receptor alkylation studies with chloroethylclonidine and 2-aminoethyl methanethiosulfonate hydrobromide. The results indicate that the alpha(2A)-AR(R) model provides a better explanation for ligand binding than does our alpha(2A)-AR(BR) model. Thus, we have made an extensive analysis of ligand binding to alpha(2A)-AR(R) and engineered mutant receptors using clonidine, para-aminoclonidine, oxymetazoline, 5-bromo-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14,304), and norepinephrine as ligands. The representative docked ligand conformation was chosen using extensive docking simulations coupled with the identification of favorable interaction sites for chemical groups in the receptor. These ligand-protein complex studies provide a rational explanation at the atomic level for the experimentally observed binding affinities of each of these ligands to the alpha(2A)-adrenergic receptor.

Animals↗

PubMed1999

Chloroethylclonidine and 2-aminoethyl methanethiosulfonate recognize two different conformations of the human alpha(2A)-adrenergic receptor.

The substituted cysteine-accessibility method and two sulfhydryl-specific reagents, the methane-thiosulfonate derivative 2-aminoethyl methanethiosulfonate (MTSEA) and the alpha(2)-adrenergic receptor (alpha(2)-AR) agonist chloroethylclonidine (CEC), were used to determine the relative accessibility of engineered cysteines in the fifth transmembrane domain of the human alpha(2A)-AR (Halpha2A). The second-order rate constants for the reaction of the receptor with MTSEA and CEC were determined with the wild type Halpha2A (cysteine at position 201) and receptor mutants containing accessible cysteines at other positions within the binding-site crevice (positions 197, 200, and 204). The rate of reaction of CEC was similar to that of MTSEA at residues Cys-197, Cys-201, and Cys-204. The rate of reaction of CEC with Cys-200, however, was more than 5 times that of MTSEA, suggesting that these compounds may interact with two different receptor conformations. MTSEA, having no recognition specificity for the receptor, likely reacts with the predominant inactive receptor conformation (R), whereas the agonist CEC may stabilize and react preferentially with the active receptor conformation (R*). This hypothesis was consistent with three-dimensional receptor-ligand models, which further suggest that alpha(2A)-AR activation may involve the clockwise rotation of transmembrane domain 5.

Adrenergic alpha-Antagonists↗

PubMed1999

The visibility of cancer on earlier mammograms in a population-based screening programme.

The aim of this study was to examine how frequently the later-round screen-detected and interval breast cancers were visible in earlier screening mammograms by retrospective review and to compare their radiological and clinicopathological features with those diagnosed by primary screening. In a population-based mammography screening programme 63,731 women aged 50-59 years were invited and 56,158 examinations were carried out in the period 1987-1992 in the Tampere area in Finland. A total of 276 breast cancers were detected, of which 131 were diagnosed on later screening rounds or were interval cancers. A retrospective review of previous screening mammograms was carried out in 130 cases by the radiologist who diagnosed the breast cancer and thus knew the exact location of the tumour, no blinded review was carried out. 43 (33%) cancers were visible, 84 (65%) were not visible and 3 (2%) not included on the mammogram in a retrospective review. Later round screen-detected cancers were statistically significantly more often visible in earlier screening mammograms (43%) than interval cancers (19%) (P = 0.002). Tumours missed by screening mammography but which were visible on retrospective review were often histologically well-differentiated and were more often diagnosed in the subsequent screening round than by clinical diagnosis as interval cancers. If all retrospectively visible interval cancers had been diagnosed by screening 19% (10/54) of the interval cancers could have been avoided. If all retrospectively visible cancers had been diagnosed at the time of false-negative screening or assessment 65% (84/130) of all patients would have benefitted from an earlier diagnosis compared with the actual figure of 31% (41/130).

Breast Neoplasms↗

PubMed1999

Incremental cost-effectiveness of double-reading mammograms.

BACKGROUND: Double reading is a widely used criterion standard in breast cancer screening despite a lack of evidence of the cost-effectiveness of the second reading. This study evaluates the incremental cost-effectiveness of such a strategy. DESIGN: Cost-effectiveness analysis: Nationwide population-based semi-annual screening program for women aged 50-59 in Finland. Participation rate was 91%. All mammograms (95,423) performed during 1990-1995 in three screening centers of the Finnish Cancer Society were read by two radiologists with gradings recorded. The effectiveness of the double reading was the difference in cancers detected in the double compared to that of the single reading. Incremental costs of the double reading for the health care and non-health care and the time costs were estimated. The main outcome measure was the incremental cost per additional cancer found as a result of the double-reading strategy. RESULTS: The total number of cancers detected with the double and single reading were 290 and 261, respectively. A significantly higher ratio of carcinoma in situ was the causative pathology in cancers detected only by the second reader. The cost per cancer detected with a single reading was US$ 18,340. The incremental cost of any additional cancer found was US$ 25,523, that is, a 39% higher cost per additional cancer found by double reading. CONCLUSIONS: The additional cost per cancer detected by double reading is not drastically higher than with single reading. However, the additional cost per life year saved may be much higher.

Breast Neoplasms↗

PubMed1998

Favorable change in mammographic parenchymal patterns and breast cancer risk factors.

The aim of our study was to estimate the incidence of favorable mammographic patterns and to assess the incidence by risk factors of breast cancer. Data relate to 1,947 women aged 40-47 years who were screened by mammography every second year and whose mammographic parenchymal pattern at initial screening was either P2 or DY (Wolfe's classification). The pattern was assessed at each screening round. The incidence of N1,P1 parenchymal pattern by risk factors was estimated. The Cox proportional hazards model was applied in univariate and multivariate analyses of the data. The incidence of N1,P1 pattern was 12.5/100 woman years among women with P2,DY pattern at the beginning of follow-up. The relative risk of N1,P1 pattern adjusted for the other risk factors for women aged 45 years or more was 1.7 [95% confidence interval (CI) 1.5-1.9] compared with younger women. The adjusted relative risk of N1,P1 pattern among women with a body mass index (BMI) of 25 or more was 2.1 (95% CI 1.6-2.8) compared with women with a BMI of less than 20; women with more than 2 pregnancies had a 30% higher adjusted relative risk (RR = 1.3, 95% CI 1.1-1.6) than women with no pregnancies. The incidence of favorable mammographic parenchymal pattern was significantly related to old age, large BMI and multiparity. The effects of age and BMI on incidences of favorable and unfavorable change potentiate each other but not that of parity.

Adult↗

PubMed1997

Structural and functional consequences of substitutions at the tyrosine 55-lysine 104 hydrogen bond in Escherichia coli inorganic pyrophosphatase.

Tyrosine 55 and lysine 104 are evolutionarily conserved residues that form a hydrogen bond in the active site of Escherichia coli inorganic pyrophosphatase (E-PPase). Here we used site-directed mutagenesis to examine their roles in structure stabilization and catalysis. Though these residues are not part of the subunit interface, Y55F and K104R (but not K104I) substitutions markedly destabilize the hexameric structure, allowing dissociation into active trimers on dilution. A K104I variant is nearly inactive while Y55F and K104R variants exhibit appreciable activity and require greater concentrations of Mg2+ and higher pH for maximal activity. The effects on activity are explained by (a) increased pK(a)s for the catalytically essential base and acid at the active site, (b) decreases in the rate constant for substrate (dimagnesium pyrophosphate) binding to enzyme-Mg2 complex vs enzyme-Mg3 complex, and (c) parallel decreases in the catalytic constant for the resulting enzyme-Mg2-substrate and enzyme-Mg3-substrate complexes. The results are consistent with the major structural roles of Tyr55 and Lys104 in the active site. The microscopic rate constant for PPi hydrolysis on either the Y55F or K104R variants increases, by a factor of 3-4 in the pH range 7.2-8.0, supporting the hypothesis that this reaction step depends on an essential base within the enzyme active site.

Biopolymers↗

PubMed1997

Relationship between immobilised artificial membrane chromatographic retention and the brain penetration of structurally diverse drugs.

Retention factors were determined for a set of 26 drugs, for which brain/blood concentration data are available, using immobilised artificial membrane (IAM) chromatography. The compound set represented acidic, basic and neutral drugs from various structural classes. The relationship between IAM retention and lipophilicity (n-octanol-water partition coefficient Koct), molecular size and acid/base character of the drugs and the relationship between brain distribution and IAM retention and the other parameters were analysed. IAM retention was increased with increases in lipophilicity and solute size, and decreased by the ionisation of acidic groups. Ionisation of basic groups had no significant effect. A three-parameter regression model with log Koct, molecular weight and an indicator parameter for the presence of carboxyl group explained 93% of the variation in log kIAM. The concentration ratio between brain and blood (log BB) was only weakly correlated with the IAM chromatographic retention or n-octanol-water partitioning. Three-parameter models taking ionisation and size into account, in addition to either log Koct or log kIAM, explained about 85% of the variation of log BB in the test set. Although IAM chromatography offers no advantage in these models, it seems to provide a better model than n-octanol-water partitioning for the membrane distribution of ionised compounds.

Animals↗